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Biomedical subjects

O Schwartz

Publications and source records attributed to O Schwartz.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pulp and periodontal healing, root development and root resorption subsequent to transplantation and orthodontic rotation: a long-term study of autotransplanted premolars.

One hundred and eighteen premolars transplanted at a stage with 3/4 to 4/4 root development with a wide open apical foramen were followed with standardized clinical and radiographic techniques for signs of pulpal and periodontal ligament healing and root development. Pulp healing, evaluated first by radiographic presence of pulp canal obliteration, appeared to be an earlier sign of pulp healing than the detection of pulp vitality with an electrometric test. Continued root growth of premolars was seen in some cases. Complete arrest of root development was usually followed by development of the missing root structure at the donor site, indicating a separation of the Hertwig's epithelial root sheath. Orthodontic rotation performed on 11 premolars induced slight surface resorption and a significant shortening of tooth length (mean 1.2 mm), compared with nontreated but transplanted control teeth. However, the extent of the apical root resorption is of minor clinical importance, and is equivalent to what has been found in previous investigations of orthodontic treatment of nontransplanted premolars. Late pulp necrosis occurred in 2 of the 11 treated cases 6 years after transplantation and 5 years after orthodontic rotation. To prevent late pulp necrosis, orthodontic rotation is recommended after periodontal healing and before total pulp canal obliteration has taken place, i.e., 3 to 9 months after transplantation.

Bicuspid↗
PubMed1995

Human immunodeficiency virus type 1 Nef induces accumulation of CD4 in early endosomes.

We have studied the fate of CD4 in CEM T cells expressing a human immunodeficiency virus type 1 HIV-1 Nef protein. Nef triggered a rapid endocytosis and a degradation of CD4, while most of the p56lck was upheld at the cell membrane. In the presence of Nef, CD4 accumulated in acidic intracellular vesicles that were not stained by antibodies against rab6, a marker of the Golgi apparatus complex. Detection of transferrin in CD4-containing vesicles showed that CD4 was trapped in early endosomes, without significant accumulation of CD4 in late endocytic compartments. Internalization pathways taken by CD4 in Nef+ cells may therefore be different from those observed after treatment with phorbol esters.

CD4 Antigens↗
PubMed1995

Human immunodeficiency virus type 1 Nef increases the efficiency of reverse transcription in the infected cell.

We have analyzed the replication of Nef+ and Nef- isogenic human immunodeficiency virus in CEM, HUT78, MT4 lymphoid, and U937 monocytic cell lines. At each passage of infected cells, we have assessed the relative infectivity of the virus particles released in culture media by measuring the number of infections units per nanogram of p24 protein. Values appeared to be 3- to 10-fold higher for the Nef+ virus than for the Nef- number The positive effect of Nef was observed regardless of the cell line, the multiplicity of infection, and the number of virus replication cycles achieved. We showed, by using cells expressing glycosylphosphatidylinositol-linked CD4, that the enhancement of virion infectivity could be dissociated from the down-regulation of cell surface CD4 also induced by Nef. The gp120-to-p24 ratio and the RNA content of virus particles produced in the presence or in the absence of Nef were equivalent. Virions bound to cell surface CD4 receptors with equal efficiencies. Equivalent reverse transcriptase activities were measured both on exogenous substrate and on particle genomic RNAs. In contrast, reverse transcription in infected cells generated 5- to 10-fold less DNA when the virions were produced in the absence of Nef, indicating that these particles performed reverse transcription in a suboptimal environment. These data suggest that the expression of Nef in virus-producing cells is required for efficient processing of the early stages of virus replication in target cells, including the internalization in an appropriate cell compartment and the uncoating of the particle.

Cell Line↗
PubMed1994

Impairment of T cell receptor-dependent stimulation in CD4+ lymphocytes after contact with membrane-bound HIV-1 envelope glycoprotein.

A CD4+ human T cell clone (SPB21) or primary blood mononuclear cells were grown in the presence of HeLa cells stably expressing functional human immunodeficiency virus type 1 envelope glycoprotein complexes at their surface. After a short cocultivation, SPB21 cells lost their ability to proliferate in response to T cell receptor (TCR) stimulations and died by apoptosis, whereas interleukin-2 stimulation was still effective. Incubation with soluble monomeric gp120 did not alter TCR responsiveness. A selective decrease in the proportion of CD4+ cells was also observed among primary lymphocytes after cocultivation and OKT3 stimulation. We propose that binding of oligomeric membrane-bound envelope glycoprotein induces a multimerization of CD4 molecules that impairs normal TCR stimulation.

Apoptosis↗
PubMed1993

Efficient antigen presentation to cytotoxic T lymphocytes by cells transduced with a retroviral vector expressing the HIV-1 Nef protein.

In the classic model of antigen processing and presentation, viral antigens must be synthesized within the cytoplasm of infected cells to be processed and presented to CD8+, MHC class I-restricted cytotoxic T lymphocytes (CTLs). We have examined the utility of a retroviral vector (pNeoNef) expressing the human immunodeficiency virus type (HIV-1)Lai Nef protein for the development of target cells to study HIV-specific CTLs. Autologous Epstein-Barr-transformed B cell lines (EBV-B cells) transduced with pNeoNef were efficiently lysed by CTL lines from donors capable of lysing EBV-B cells infected with a recombinant vaccinia virus (rVV) expressing Nef. Also, the transduced cells were efficient stimulator cells for the generation of Nef-specific CTL lines. The CTL lines thus generated recognized the same epitopes as CTL lines from the same donor generated by nonspecific stimulation. The use of similar cell lines transduced with retroviral vectors expressing HIV proteins may be useful in the study of CTLs in HIV-infected donors and in the study of the ability of candidate vaccines, including rVV, to induce HIV-specific CTLs. As antigen-presenting cells, the cell lines may be useful in the generation of antigen-specific CTL lines.

Amino Acid Sequence↗
PubMed1993

Reduced cell surface expression of processed human immunodeficiency virus type 1 envelope glycoprotein in the presence of Nef.

nef genes from two laboratory grown human immunodeficiency virus type 1 (HIV-1) strains and from two proviruses that had not been propagated in vitro were introduced into CD4+ lymphoblastoid CEM cells. The stable expression of all four Nef proteins was associated with an almost complete abrogation of CD4 cell surface localization. The consequences of the presence of Nef on gp160 cleavage, gp120 surface localization, and envelope-induced cytopathic effect were examined in CEM cells in which the HIV-1 env gene was expressed from a vaccinia virus vector. The presence of Nef did not modify the processing of gp160 into its subunits but resulted in a significant decrease of cell surface levels of gp120, associated with a dramatic reduction of the fusion-mediated cell death. Surface levels of mutant envelope glycoproteins unable to bind CD4 were not altered in Nef-expressing cells, suggesting that the phenomenon was CD4 dependent. The intracellular accumulation of fully processed envelope glycoproteins could significantly delay the cytopathic effect associated with envelope surface expression in HIV-infected cells and may be relevant to the selective advantage associated with Nef during the in vivo infectious process.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Activation pathways and human immunodeficiency virus type 1 replication are not altered in CD4+ T cells expressing the nef protein.

While recent studies in Rhesus monkeys have pointed out the importance of an intact nef gene for the development of acquired immunodeficiency syndrome (AIDS), no biological function has been so far unambiguously attributed to its product. Since Nef has been described to possess GTP-binding properties and to down-regulate CD4 cell surface expression, we looked for evidences of Nef interfering with the transduction of activating signals in human CD4+ T cells. We used a murine leukemia retroviral vector to express the HIV-1BRU nef gene in two permanent tumoral T-cell lines (CEM and Jurkat) and in two nonimmortalized, interleukin-2 (IL2)-dependent, T-cell clones. The single copy recombinant provirus integrated in the genome of these cells directed the synthesis of a 27-kD protein with a half-life greater than 5 h. The levels of expression of cell surface molecules involved in T-cell functions (CD4, CD3, CD28, CD29, IL-2 receptor) were not modified in cell populations expressing Nef. In immunocompetent T-cell clones, cell proliferation and lymphokine production in response to activating stimuli (IL-2, alloantigens, phorbol esters, or antibodies directed against CD2, CD3, CD4, CD28) remained unmodified. Moreover, the presence of Nef did not change the kinetics of human immunodeficiency virus (HIV) infection.

3T3 Cells↗
PubMed1991

Lipophilic glycosyl phosphotriester derivatives of AZT: synthesis, NMR transmembrane transport study, and antiviral activity.

Phosphate derivatives of AZT esterified with a carbohydrate (D-glucose, D-mannose, and ethyl D-mannopyranoside) and a hexadecyl chain were prepared from glucose 6-phosphate and D-mannose precursors. The 31P NMR study of the mannosyl phosphotriester series in the presence of large unilamellar vesicles demonstrated either an interaction with the external lipid layer or a transmembrane transport into the intravesicular interface. The antiviral activity, measured by the inhibition of cytopathogenicity on different infected cells and of reverse transcriptase activity in the supernatant of cultures, appeared to be comparable to that of AZT, in the micromolar range.

Antiviral Agents↗
PubMed1991

Architectural organization of human oral epithelium as visualized by keratin staining pattern in tobacco-associated leukoplakias.

The keratin staining pattern in clinical normal buccal mucosa in smokers and non-smokers and in tobacco-associated leukoplakias histologically characterized by the chevron type of keratinization were studied. No differences in keratin staining pattern were found in normal buccal mucosa in smokers and non-smokers. In the tobacco-associated leukoplakias we found distinct differences in staining pattern between areas overlying connective tissue papillae and epithelial ridge areas indicating a lateral organization of oral epithelium related to the ridge system. It seems possible to explain this pattern in terms of current hypotheses of the proliferative conditions in squamous epithelia as previously studied in detail in the epidermis and tongue filiform papillae. We conclude, that our results confirm the presence of subpopulations of suprabasal and basal cells and support the presence of proliferative units in oral epithelium. Furthermore, smoking does not seem to influence the keratin staining pattern in clinically normal buccal mucosa.

Adult↗
PubMed1990

A microtransfection method using the luciferase-encoding reporter gene for the assay of human immunodeficiency virus LTR promoter activity.

A microtransfection method, using either the DEAE-dextran or the Ca.phosphate procedure has been developed. A plasmid expressing the luciferase-encoding gene under the control of the human immunodeficiency virus (HIV) LTR promoter was constructed. Transfections were performed in 96-well plates, allowing statistical evaluation of the results. This microtransfection method requires the use of 100- to 1000-fold less plasmid and cells than in a conventional chloramphenicol acetyl transferase (CAT) assay. A Luciferase index which takes into account cell viability after transfection has been defined using a semi-automated absorbance assay. A 20-h incubation period post-transfection is sufficient for optimal results. Basal long terminal repeat activity and autologous Tat transactivation were studied in various lymphoid, monocytic and adherent human cell lines. Infection of microtransfected cells by HIV activated luc expression. This assay can thus also be used for rapid detection and quantitation of HIV. Antiviral activities of drugs can be assessed in a two-day test.

Cells, Cultured↗
PubMed1990

Reinnervation of autotransplanted teeth. A histological investigation in monkeys.

The reinnervation of 8 autotransplanted teeth in 4 green vervet monkeys (Ceropithecus aethiops) was examined. The lateral maxillary incisors of each animal were extracted and transplanted to the contralateral side. The root formation was incomplete with an open apical foramen. The monkeys were killed 1, 2 or 4 months after transplantation and examined histologically by a S-100 monoclonal antibody staining. A few single nerve fibres could be seen 1 month after transplantation. After 2 months, several nerve bundles could be detected throughout the whole pulp. After 4 months, a larger number of nerve bundles, comparable to the densely innervated dental pulp of non-transplanted teeth, could be seen throughout the whole pulp.

Animals↗
PubMed1990

A long-term study of 370 autotransplanted premolars. Part II. Tooth survival and pulp healing subsequent to transplantation.

The purpose of the present investigation was to determine the long-term prognosis of autotransplanted premolars with respect to tooth survival and pulpal healing. The material consisted of 195 patients aged 7 to 35 years, with a total of 370 autotransplanted premolars with observation period ranged from 1 to 13 years. Teeth transplanted with incomplete and complete root formation showed 95 per cent and 98 per cent long-term survival respectively: Pulp healing as evaluated by sensibility testing and radiographic signs of partial pulp canal obliteration was usually verified 6 months after transplantation. The frequency of pulpal healing (versus pulp necrosis), appeared to be closely related to stage of root development at time of transplantation. Teeth transplanted with incomplete and complete root formation showed 96 per cent and 15 per cent pulp healing respectively. Another and associated factor which could equally well predict pulpal healing was the diameter of the apical foramen of the graft. Finally, in teeth with completed root formation, the use of bursa with internal cooling and no extra-alveolar storage prior to transplantation seemed to increase the chance for pulpal healing. The present study indicates, that the size of the apical foramen and possibly the avoidance of bacterial contamination during the surgical procedure are explanatory factors for pulpal healing.

Adolescent↗
PubMed1990

A long-term study of 370 autotransplanted premolars. Part III. Periodontal healing subsequent to transplantation.

The purpose of the present investigation was to determine the long-term prognosis of autotransplanted premolars with respect to periodontal healing. The subjects consisted of 195 patients aged 7 to 35 years, with a total of 370 autotransplanted all operated and followed with a standard technique. The observation period ranged from 1 to 13 years. Periodontal healing as demonstrated radiographically was complete in most cases after 8 weeks. Root resorption occurring after transplantation was divided into surface-, inflammatory- and replacement resorption (ankylosis). Root resorption occurred in 52 of the transplanted teeth and was usually diagnosed within 6 months. Root resorption was found to be significantly related to increasing stage of root development and the stage of eruption at the time of transplantation. Subsequent orthodontic movement of teeth with completed root formation at the time of transplantation resulted in a slight increase in the frequency of both surface and inflammatory resorption. The present study indicates that trauma to the PDL of the transplant is the explanatory factor for the development of root resorption.

Adolescent↗
PubMed1990

A long-term study of 370 autotransplanted premolars. Part I. Surgical procedures and standardized techniques for monitoring healing.

Tooth autotransplantation has recently become a method of treating certain orthodontic problems. Over a 13-year period 370 premolar transplants were monitored by electrometric pulp sensibility testing and radiographic examination for pulp and periodontal ligament healing as well as root growth. This article describes the surgical technique as well as the precision of sensibility testing and radiographic examination for evaluating transplant healing. The sensibility response was found markedly related to the stage of tooth development but not to the type of premolar. The precision of sensibility testing (i.e. deviation of two consecutive measurements at a few weeks' interval) was found to range from 15-36 per cent for the different stages. Film holders were used to standardize the intraoral radiographic exposures. The precision percentage for the measuring technique of tooth length and crown width based on a single radiograph read twice (reading error) ranged from 1.1 to 1.8 with only small variations among the different types of premolar. The precision percentage of the radiographic exposure technique evaluated from two consecutive radiographs (measuring plus exposure error) was found to range from 1.2 to 4.2, again with small variations among the different premolars. The accuracy of the radiographic technique (i.e. deviation of radiographically determined tooth dimensions from the true values) was found to range from 2.0 to 2.9 with only small variation between the various types of premolar. In conclusion the evaluation of electrometric sensibility testing should take into account the stage of root formation of premolars.

Adolescent↗
PubMed1990

Transmission electron microscopy of supra-alveolar periodontal healing of auto- and allotransplanted teeth in monkeys.

An ultrastructural study of the supra-alveolar periodontal healing of auto- and allotransplanted teeth was performed in 4 immunologically unmatched green Vervet monkeys. Eight mature incisors were either auto- or allotransplanted. Non-transplanted adjacent incisors served as controls. Prior to transplantation the teeth were endodontically treated extraorally. Eight weeks after transplantation, biopsies including part of the tooth and the adjacent supra-alveolar tissues were taken, fixed, decalcified and processed for electron microscopy. A thin electron dense layer covered the root surface of the autotransplanted teeth. Most collagen fibres inserted into this electron-dense border, as well as into the underlying cementum. A similar relationship between the fibres and root surface was found in controls. On the allotransplanted teeth a layer of electron-dense granular material covered the root surface in the supra-alveolar area. Collagen fibres inserting into the electron-dense border were frequently observed. Fibroblasts were the predominant cell type in the connective tissue adjacent to all transplanted teeth. In autotransplants 2 morphotypes of fibroblasts were observed: 1) cells with dilated endoplasmic reticulum and swollen mitochondria; and 2) cells with normal characteristics of protein synthesis and secretion. The fibroblasts of the allografts were predominantly cells with dilated endoplasmic reticulum and swollen mitochondria. The results indicated some similarities in the healing between the root surface and connective tissue in the supra-alveolar portion of the roots of auto- and allotransplanted teeth.

Animals↗
PubMed1990

Export and one-step purification from Escherichia coli of a MalE-CD4 hybrid protein that neutralizes HIV in vitro.

The 177 N-terminal amino acids of CD4, the receptor of the human immunodeficiency virus (HIV), have been expressed in Escherichia coli as genetic fusions to the periplasmic maltose-binding protein (MalE) from this organism. A large fraction of the hybrid proteins can be released from the periplasm by osmotic shock and purified in one step on a cross-linked amylose column eluted with maltose under mild conditions. One hybrid protein binds HIV envelope protein gp160 and neutralizes the virus in vitro. This provides the first example of the production and one-step purification of an active form of an eukaryotic protein by fusion to MalE. The use of this system for mass screening of CD4 mutants, high-scale production of the hybrid protein for structural studies on CD4, testing antiviral compounds, and therapeutic assays is discussed.

ATP-Binding Cassette Transporters↗
PubMed1990

[Carcinoma in situ of soft palate].

A case of carcinoma in situ in the soft palate in a 46-year-old man, heavy smoker, is presented. Six month's previously the patients own dentist discovered a rash in the soft palate, but no biopsy was taken until 6 months later when the patient was referred to the Dental Department, University Hospital, Copenhagen. The patient was referred to an oncologic department for evaluation. As radiation therapy was not indicated, surgery was performed. This included removal of the soft palate, tonsil and tonsil fossae. The patient had a palate plate done to relieve problems with swallowing. Patients with a long history of heavy smoking and oral lesions with suspicion for malignancy should always immediately after recognition of the lesion have more intensive examination and this should include a biopsy to establish a reliable diagnosis.

Carcinoma in Situ↗